The effects of chronic administration of aflatoxin B1 (AFB1) on liver
drug metabolism enzymes were measured in New Zealand rabbits divided i
nto three groups of 5 animals, each receiving over 5 days either arabi
c gum or AFB1 in arabic gum at a daily oral dose of 0.05 or 0.10 mg/kg
. These treatments did not lead to any lethality in any of the treated
groups but the body weight gain was altered. Biochemical exploration
of plasma components revealed a dose-dependent hepatotoxicity characte
rized by cytolysis and cholestasis. At 0.10 mg/kg/day of AFB1, signifi
cant decreases were observed in total liver microsomal cytochrome P450
, several P450-dependent monooxygenase activities, all individual P450
isoenzymes levels analysed by Western-blotting and glutathione S-tran
sferase activities. By contrast, at 0.05 mg/kg/day of AFB1, even thoug
h total cytochrome P450 was decreased by 30%, only P450 1A1 and 3A6 is
oenzymes, and aniline hydroxylation, pentoxyresorufin O-depentylation,
aminopyrine, erythromycin, ethylmorphine and dimethylnitrosamine N-de
methylations were affected. In the same animal group, the only glutath
ione S-transferase accepting CDNB (1-chloro-2,4-dinitrobenzene) as sub
strate was decreased by 22%. UDP-glucuronyltransferase accepting p-nit
rophenol as substrate was increased in both groups of animals (33-62%)
. The mechanisms that could contribute to the observed changes in drug
metabolizing enzymes are discussed.